Sodium channelopathies in skeletal muscle and brain

Ion channel disorders are rare inherited diseases providing interesting models to study dysfunction of excitability in vivo and in vitro. The first socalled ‘channelopathies’ identified were skeletal muscle diseases, the myotonias and hyperkalemic periodic paralysis (HyperPP), which are sodium or chloride channel disorders. Within the last 5–10 years, complementary genetic and electrophysiological investigations led to the continuously growing list of channelopathies. Beside skeletal muscle, the channelopathies affect in particular other excitable tissues such as heart muscle and the nervous system. Typical examples are inherited cardiac arrythmias, episodic ataxias, familial hemiplegic migraine and some familial idiopathic epilepsy syndromes, but also kidney stones or hypertension can be caused by ion channel defects. The responsible genes encode for subunits of sodium, potassium, calcium or chloride channels which are gated by membrane voltage, ligands such as acetylcholine or γ-amino-butyric-acid (GABA) or other factors (for a recent comprehensive review see LehmannHorn and Jurkat-Rott 1999). This article will focus on the pathophysiological concepts of the sodium channelopathies found in skeletal muscle and brain, namely HyperPP, paramyotonia congenita (PC), potassium aggravated myotonia (PAM), hypokalemic periodic paralysis type 2 (HypoPP2), generalized epilepsy with febrile seizures plus (GEFS) and severe myoclonic epilepsy of infancy (SMEI).